Preparation And Quality Control Of Fast-dissolving Oral Films Of Folic Acid

Objetive:Folic acid is one of the most important vitamin drugs,which is clinically used to treat the folic acid deficiency caused by a variety of reasons,reduce neural tube defects in newborns,and assist in the treatment of malignant anemia.In recent years,people have been discovered many new therapeutic effects of folic acid.Besides effective treatment for H type hypertension,atrophic gastritis,and osteoarthritis,folic acid can also be applied to the adjuvant treatment and diagnosis of various cancers,such as gastric cancer,liver cancer and colorectal cancer.Its market prospect have highly potential.At present,there are only traditional formulations of folic acid preparation in the domestic market,such as tablets,capsules,granules and so on.The purpose of this project is to design a fast-dissolving oral films of folic acid,which is thin,flexible and more easily swallow,and has accurate dose and rapid disintegration.So the children,the elderly and the patients with dysphagia can be administered independently,to improve the compliance of medication.Simultaneously,the quality control method is established to ensure that the established method is accurate,reliable,simple and convenient,and the stability of the preparation is investigated.Methods:In this subject,the central composite design and response surface methodology combined with the single factor test were used to screen and optimize prescription of fast-dissolving oral films of folic acid.The use of single factor test was to determine the types and approximate amounts of film-forming polymers,plasticizers and addition agents used in the prescription.The main evaluation refers to the appearance,thickness,performance of de-filming,folding endurance and dissolution time limit of membrane agents.In addition,the central composite design and response surface methodology was combined with the corresponding experimental design methods to make a scientific analysis of the key factors effecting prescription.The dosage of the excipients of the fast-dissolving oral films of folic acid was optimized by examining the folding endurance and dissolution time limit.At the same time,high performance liquid chromatography?HPLC?was used to study the quality control of fast-dissolving oral films of folic acid.While referring to China Pharmacopoeia?2015?,"Food safety national standard Food additive Folic acid"?GB 15570-2010?and the actual situation,an accurate and reliable quality control method was established.Stress testing,accelerated testing and long-term testing provide a support basis for the selection and optimization of the prescription,the improvement of the preparation process,the formulation of quality control standards,the packing and transportation,and the storage conditions,etc.Results:The ultimate prescription were determined to be as follows.The folic acid 0.4 mg;HPMC E15 8 mg;propylene glycol 3.5 mg;?-CD 8 mg;sucralose 0.2mg;DL-malic acid 0.8 mg and sweet orange flavor 0.1 mg.HPLC conditions of folic acid was determined as:a silica gel column Innoval ODS-2 C18 reverse column?250mm×4.6mm,5?m?was choiced,and mobile phase was methanol?0.054 mol/L KH₂PO₄?ammonia to adjust the pH of 6.3±0.1??8:92?.The flow rate was 1.0 mL/min.Detection wavelength was set as?=254nm.Column temperature was?30±1??.In this chromatographic conditions,concentration range of folic acid showed good linearity at 40.0²60.0?g/L.The accuracy and precision was good.This method was accurate and with high specificity,which can effectively determine the content and content uniformity of the sample.Conclusion:In this project,prescription and technique of fast-dissolving oral films were screened the optimized.The films has good properties and uniform content.And it can disintegrate rapidly,so the preparation conforms to the needs of the dosage form.The quality control method was special,highly sensitive,accurate,reliable,simple.It can be used for the determination of content and uniformity of folic acid,and other related inspection.